Maintenance Treatment for Ovarian Carcinoma in Remission by an Antiangiogenic Treatment Strategy

Maintenance Treatment for Ovarian Carcinoma in Remission by an Antiangiogenic Treatment Strategy With Metronomic/Oral Chemotherapy (Cytophosphan Combined With Low-dose Methotrexate)and COX-2 Inhibition (Celecoxib)

Preclinical studies showed that metronomic chemotherapy can induce tumor regression secondary to apoptosis of the tumor blood vessels. This effect was increased by combining metronomic chemotherapy with anti-angiogenic drugs. Metronomic chemotherapy has already proved clinical effects too, especially on patients with breast or prostate carcinoma. This study is aimed to test the efficacy of an experimental metronomic chemotherapy regimen in a cohort of patients with ovarian cancer. Patients will receive the proposed regimen as maintenance treatment following response induction by the conventional maximal tolerated dose (MTD) regimen of Carboplatin and Paclitaxel. Our regimen will include Cytophosphan combined with two agents which are expected to act as indirect angiogenic inhibitors: (a) celecoxib, as a selective COX-2 inhibitor and (b) low-dose Methotrexate, as successfully practiced for suppressing the inflammatory manifestations of rheumatoid arthritis. All components of our regimen will be administered orally and continuously for one year based on the hypothesis that its anti-angiogenic properties will be able to suppress the recovery of residual disease, thus extending the time to progression (TTP), and possibly the overall survival as well.

Study Overview

• Status: Terminated
• Conditions: Ovarian Carcinoma
• Intervention / Treatment: Drug: Cytophosphan, Celecoxib, Methotrexate

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Afula, Israel, 18101
    • Haemek Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Histologic proof of papillary-serous ovarian cancer or 1ary peritoneal carcinomatosis.
2. Histological grade III.
3. Original disease in stage III.
4. ECOG performance status: 0-2.
5. Age: 20-80 years.
6. Previous chemotherapy with paclitaxel and carboplatin (only).
7. Previous cyto-reductive surgery.
8. Clinical Complete Response (both physically and by imaging).
9. CA 125 should be either normalized (in at least 50 patients) or while still in decreasing values at monthly measurements.
10. CBC at normal values or with any toxicity at a grade limited to I by NCIC-CTC.
11. Liver and renal functions < 1.5 upper normal limits (UNL) by SMA.
12. The patient's signature on the informed consent.

Exclusion Criteria:

1. Mucinous type ovarian carcinoma.
2. Histological Grade I-II.
3. Current continuous treatment by steroids or by NSAIDs, or by anti-coagulants for "non protocol" reasons.
4. Previous history of active peptic ulcer.
5. Current participation in any other treatment study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metronomic Chemoterapy; Maintenance Treatment for Ovary Carcinoma by Metronomic Chemotherapy	Drug: Cytophosphan, Celecoxib, Methotrexate; Metronomic Chemotherapy as maintenance treatment for patients with Ovarian Cancer; Cytophosphan tab 50 mg -1x1 per day, continuous; Celecoxib tab 200 mg - 1x2 per day, continuous; Methotrexate tab 2.5 mg - 1x2 per day, 2 days weekly

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Progression	Median time to progression of the cohort will be compared with equivalent measure in the literature.	18 months

Collaborators and Investigators

• Sponsor: HaEmek Medical Center, Israel
• Investigators: Study Director: David Loven, M.D., HaEmek Medical Center, Oncology Unit

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): April 1, 2013
• Study Completion (Actual): April 1, 2013

Study Registration Dates

• First Submitted: August 1, 2010
• First Submitted That Met QC Criteria: August 4, 2010
• First Posted (Estimate): August 5, 2010

Study Record Updates

• Last Update Posted (Estimate): June 23, 2015
• Last Update Submitted That Met QC Criteria: June 21, 2015
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Carcinoma; Chemotherapy; Ovary; Maintenance; overall survival; Time to Progression; Metronomic
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Carcinoma; Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Dermatologic Agents; Reproductive Control Agents; Cyclooxygenase 2 Inhibitors; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Cyclophosphamide; Celecoxib; Methotrexate
• Other Study ID Numbers: 0082-09-EMC